tbuckley/cabot-search huggingface dataset:
Inhibitor of <scp>NF‐κB</scp> Kinase Subunit ε Contributes to Neuropsychiatric Manifestations in <scp>Lupus‐Prone</scp> Mice Through Microglial Activation
Authors: Kohei Karino, Michihito Kono, Shuhei Takeyama, Yuki Kudo, Masatoshi Kanda, Nobuya Abe, Kuniyuki Aso, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Olga Amengual, Tatsuya Atsumi
Journal: Arthritis & Rheumatology (2022)

Objective Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30–40% of lupus patients and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue‐resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. This study was undertaken to explore new therapeutic targets for NPSLE focusing on microglia. Methods RNA sequencing of microglia in MRL/ lpr , lupus‐prone mice, as well as that of microglia cultured in vitro with cytokines were performed. A candidate gene, which could be a therapeutic target for NPSLE, was identified, and its role in microglial activation and phagocytosis was investigated using specific inhibitors and small interfering RNA. The effect of intracerebroventricular administration of the inhibitor on the behavioral abnormalities of MRL/ lpr was also evaluated. Results Transcriptome analysis revealed the up‐regulation of Ikbke , which encodes the inhibitor of NF‐κB kinase subunit ɛ (IKBKε) in both microglia from MRL/ lpr mice and cytokine‐stimulated microglia in vitro. Intracerebroventricular administration of an IKBKε inhibitor ameliorated cognitive function and suppressed microglial activation in MRL/ lpr mice. Mechanistically, IKBKε inhibition reduced glycolysis, which dampened microglial activation and phagocytosis. Conclusion These findings suggest that IKBKε plays a vital role in the pathogenesis of NPSLE via microglial activation, and it could serve as a therapeutic target for NPSLE.
Treatment of Genetic Diseases With CRISPR Genome Editing
Authors: Matthew J. Kan, Jennifer A. Doudna
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect
Authors: Haiyan Zhou, Ying Hong, Mariacristina Scoto, Alison Thomson, Emma Pead, Tom MacGillivray, Elena Hernandez-Gerez, Francesco Catapano, Jinhong Meng, Qiang Zhang, Gillian Hunter, Hannah K. Shorrock, Thomas K. Ng, Abedallah Hamida, Mathilde Sanson, Giovanni Baranello, Kevin Howell, Thomas H. Gillingwater, Paul Brogan, Dorothy A. Thompson, Simon H. Parson, Francesco Muntoni
Journal: Journal of Clinical Investigation (2022)

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment.
Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden
Authors: Andreas Rillig, Katrin Borof, Günter Breithardt, A. John Camm, Harry J.G.M. Crijns, Andreas Goette, Karl-Heinz Kuck, Andreas Metzner, Panos Vardas, Eik Vettorazzi, Karl Wegscheider, Antonia Zapf, Paulus Kirchhof
Journal: Circulation (2022)

The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known.
A Randomized, <scp>Placebo‐Controlled</scp> Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings
Authors: John K. Botson, Kenneth Saag, Jeff Peterson, Naval Parikh, Stephen Ong, Dan La, Karon LoCicero, Katie Obermeyer, Yan Xin, Jason Chamberlain, Brian LaMoreaux, Supra Verma, Stephen Sainati, Suneet Grewal, Amar Majjhoo, John R. P. Tesser, Michael E. Weinblatt
Journal: Arthritis & Rheumatology (2022)

Objective To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo‐controlled, double‐blind trial. Methods This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate &lt;40 ml/minute/1.73 m 2 . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate &lt;6 mg/dl for ≥80% of visits during weeks 20–24). Efficacy was evaluated in all randomized patients (intent‐to‐treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose. Results A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between‐group difference 32.3% [95% confidence interval 16.3%, 48.3%]) ( P &lt; 0.0001 for between‐group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) ( P &lt; 0.001). Antidrug antibody positivity was also lower in the MTX group. Conclusion MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.
Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes
Authors: Felicity Newell, Peter A. Johansson, James S. Wilmott, Katia Nones, Vanessa Lakis, Antonia L. Pritchard, Serigne N. Lo, Robert V. Rawson, Stephen H. Kazakoff, Andrew J. Colebatch, Lambros T. Koufariotis, Peter M. Ferguson, Scott Wood, Conrad Leonard, Matthew H. Law, Kelly M. Brooks, Natasa Broit, Jane M. Palmer, Kasey L. Couts, Ismael A. Vergara, Georgina V. Long, Andrew P. Barbour, Omgo E. Nieweg, Brindha Shivalingam, William A. Robinson, Jonathan R. Stretch, Andrew J. Spillane, Robyn P.M. Saw, Kerwin F. Shannon, John F. Thompson, Graham J. Mann, John V. Pearson, Richard A. Scolyer, Nicola Waddell, Nicholas K. Hayward
Journal: Cancer Discovery (2022)

Abstract Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation; uveal melanoma occurs in the eyes; mucosal melanoma occurs in internal mucous membranes; and acral melanoma occurs on the palms, soles, and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNA sequencing for subsets of tumors. Uveal melanoma is genomically distinct from other melanoma subtypes, harboring the lowest tumor mutation burden and with significantly mutated genes in the G-protein signaling pathway. Most cutaneous, acral, and mucosal melanomas share alterations in components of the MAPK, PI3K, p53, p16, and telomere pathways. However, the mechanism by which these pathways are activated or inactivated varies between melanoma subtypes. Additionally, we identify potential novel germline predisposition genes for some of the less common melanoma subtypes. Significance: This is the largest whole-genome analysis of melanoma to date, comprehensively comparing the genomics of the four major melanoma subtypes. This study highlights both similarities and differences between the subtypes, providing insights into the etiology and biology of melanoma. This article is highlighted in the In This Issue feature, p. 2711
Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC
Authors: Marta Pérez-Hernández, Chantal J.M. van Opbergen, Navratan Bagwan, Christoffer Rasmus Vissing, Grecia M. Marrón-Liñares, Mingliang Zhang, Estefania Torres Vega, Andrea Sorrentino, Lylia Drici, Karolina Sulek, Ruxu Zhai, Finn B. Hansen, Alex Hørby Christensen, Søren Boesgaard, Finn Gustafsson, Kasper Rossing, Eric M. Small, Michael J. Davies, Eli Rothenberg, Priscila Y. Sato, Marina Cerrone, Thomas Hartvig Lindkær Jensen, Klaus Qvortrup, Henning Bundgaard, Mario Delmar, Alicia Lundby
Journal: Circulation (2022)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the
Early vs Standard Approach to Tracheostomy and Functional Outcome Among Patients With Severe Stroke Receiving Mechanical Ventilation
Authors: Yanfei Shen, Jing Yan, Guolong Cai
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Infant gut microbiota restoration: state of the art
Authors: Katri Korpela, Willem M. de Vos
Journal: Gut Microbes (2022)

The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.
Targeting two distinct epitopes on human CD73 with a bispecific antibody improves anticancer activity
Authors: Odd L Gammelgaard, Mikkel G Terp, Christian Renn, Aran F Labrijn, Oliver Hamaker, Aaraby Y Nielsen, Henriette Vever, Soren WK Hansen, Morten F Gjerstorff, Christa E Müller, Paul WHI Parren, Henrik J Ditzel
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immunosuppressive extracellular adenosine is generated by the enzymatic activity of CD73. In preclinical models, antibodies (Abs) targeting different epitopes on CD73 exert anticancer activity through distinct mechanisms such as inhibition of enzymatic activity, engagement of Fc receptors, and spatial redistribution of CD73. Using controlled Fab arm exchange, we generated biparatopic bispecific antibodies (bsAbs) from parental anti-CD73 Abs with distinct anticancer activities. The resulting anticancer activity was evaluated using in vitro and in vivo models. We demonstrate that different anticancer activities can be combined in a biparatopic bsAb. Remarkably, the bsAb significantly improved the enzyme inhibitory activity compared with the parental Abs, which led to neutralization of adenosine-mediated T-cell suppression as demonstrated by proliferation and interferon gamma (IFN-γ) production and prolonged survival of tumor-bearing mice. Additionally, the bsAb caused more efficient internalization of cell surface CD73 and stimulated potent Fc-mediated engagement of human immune effector cells in vitro and in vivo. Our data collectively demonstrate that complementary anticancer mechanisms of action of distinct anti-CD73 Abs can be combined and enhanced in a biparatopic bsAb. The multiple mechanisms of action and superior activity compared with the monospecific parental Abs make the bsAb a promising candidate for therapeutic targeting of CD73 in cancer. This concept may greatly improve future Ab design.
Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Alexander P J Vlaar, Martin Witzenrath, Pieter van Paassen, Leo M A Heunks, Bruno Mourvillier, Sanne de Bruin, Endry H T Lim, Matthijs C Brouwer, Pieter R Tuinman, José F K Saraiva, Gernot Marx, Suzana M Lobo, Rodrigo Boldo, Jesus A Simon-Campos, Alexander D Cornet, Anastasia Grebenyuk, Johannes M Engelbrecht, Murimisi Mukansi, Philippe G Jorens, Robert Zerbib, Simon Rückinger, Korinna Pilz, Renfeng Guo, Diederik van de Beek, Niels C Riedemann, Alexander P.J. Vlaar, Martin Witzenrath, Pieter van Paassen, Leo M.A. Heunks, Bruno Mourvillier, Sanne de Bruin, Endry H.T. Lim, Matthijs C. Brouwer, Pieter R. Tuinman, José Francisco K. Saraiva, Gernot Marx, Suzana Lobo, Rodrigo Boldo, Jesus Simon-Campos, Alexander D. Cornet, Anastasia Grebenyuk, Johannes Engelbrecht, Murimisi Mukansi, Philippe G. Jorens, Robert Zerbib, Simon Rückinger, Korinna Pilz, Renfeng Guo, Diederik van de Beek, Niels C. Riedemann, Pierre Bulpa, Fabio S. Taccone, Greet Hermans, Marc Diltoer, Michael Piagnerelli, Nikolaas De Neve, Antonio T. Freire, Felipe D. Pizzol, Anna Karolina Marinho, Victor H. Sato, Clovis Arns da Cunha, Mathilde Neuville, Jean Dellamonica, Djillali Annane, Antoine Roquilly, Jean Luc Diehl, Francis Schneider, Jean Paul Mira, Jean Baptiste Lascarrou, Luc Desmedt, Claire Dupuis, Carole Schwebel, Guillaume Thiéry, Matthias Gründling, Marc Berger, Tobias Welte, Michael Bauer, Ulrich Jaschinski, Klaus Matschke, Roberto Mercado-Longoria, Belinda Gomez Quintana, Jorge Alberto Zamudio-Lerma, Juan Moreno Hoyos Abril, Angel Aleman Marquez, Peter Pickkers, Luuk Otterspoor, Luis Hercilla Vásquez, Carlos Rafael Seas Ramos, Alejandro Peña Villalobos, Gonzalo Gianella Malca, Victoria Chávez, Victor Filimonov, Vladimir Kulabukhov, Pinak Acharya, Sjoerd A.M.E.G. Timmermans, Matthias H. Busch, Floor L.F. van Baarle, Rutger Koning, Liora ter Horst, Nora Chekrouni, Thijs M. van Soest, Marleen A. Slim, Lonneke A. van Vught, Rombout B.E. van Amstel, Sabine E. Olie, Ingeborg E. van Zeggeren, Marcel C.G. van de Poll, Claus Thielert, Dorothee Neukirchen
Journal: The Lancet Respiratory Medicine (2022)
METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma
Authors: Yang Pan, Akiko Suga, Itaru Kimura, Chojiro Kimura, Yuriko Minegishi, Mao Nakayama, Kazutoshi Yoshitake, Daisuke Iejima, Naoko Minematsu, Megumi Yamamoto, Fumihiko Mabuchi, Mitsuko Takamoto, Yukihiro Shiga, Makoto Araie, Kenji Kashiwagi, Makoto Aihara, Toru Nakazawa, Takeshi Iwata
Journal: Journal of Clinical Investigation (2022)

Normal-tension glaucoma (NTG) is a heterogeneous disease characterized by retinal ganglion cell (RGC) death leading to cupping of the optic nerve head and visual field loss at normal intraocular pressure (IOP). The pathogenesis of NTG remains unclear. Here, we describe a single nucleotide mutation in exon 2 of the methyltransferase-like 23 (METTL23) gene identified in 3 generations of a Japanese family with NTG. This mutation caused METTL23 mRNA aberrant splicing, which abolished normal protein production and altered subcellular localization. Mettl23-knock-in (Mettl23+/G and Mettl23G/G) and -knockout (Mettl23+/- and Mettl23-/-) mice developed a glaucoma phenotype without elevated IOP. METTL23 is a histone arginine methyltransferase expressed in murine and macaque RGCs. However, the novel mutation reduced METTL23 expression in RGCs of Mettl23G/G mice, which recapitulated both clinical and biological phenotypes. Moreover, our findings demonstrated that METTL23 catalyzed the dimethylation of H3R17 in the retina and was required for the transcription of pS2, an estrogen receptor α target gene that was critical for RGC homeostasis through the negative regulation of NF-κB-mediated TNF-α and IL-1β feedback. These findings suggest an etiologic role of METTL23 in NTG with tissue-specific pathology.
Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study
Authors: Ofra Amir, Yair Goldberg, Micha Mandel, Yinon M Bar-On, Omri Bodenheimer, Laurence Freedman, Nachman Ash, Sharon Alroy-Preis, Amit Huppert, Ron Milo
Journal: The Lancet Infectious Diseases (2022)
Correction: Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells
Journal: Journal for ImmunoTherapy of Cancer (2022)

In the section titled 'Induced pluripotent stem cell-derived NK cell therapies', The sentence 'For instance, CAR-NK cells derived from iPSCs targeting mesothelin showed strong in vivo responses in mouse A1847 ovarian cancer and outperformed PB-NK cell therapy' has had the phrase 'mouse A1847 ovarian cancer' updated to 'human A1847 ovarian cancer'.
Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial
Authors: Jamie E. Chaft, Filiz Oezkan, Mark G. Kris, Paul A. Bunn, Ignacio I. Wistuba, David J. Kwiatkowski, Dwight H. Owen, Yan Tang, Bruce E. Johnson, Jay M. Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S. Shames, Chris Rivard, Eric Toloza, Eric B. Haura, Ciaran J. McNamee, G. Alexander Patterson, Saiama N. Waqar, Valerie W. Rusch, David P. Carbone, Saiama N. Waqar, Elaine Shum, Misako Nagasaka, Marianna Koczywas, Edward B. Garon, David J. Finley, David R. Camidge, Jennifer W. Carlisle, Justin D. Blasberg
Journal: Nature Medicine (2022)

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.